PUBLICATION
ELABELA - APJ axis protects from pressure overload heart failure and Angiotensin II-induced cardiac damage
- Authors
- Sato, T., Sato, C., Kadowaki, A., Watanabe, H., Ho, L., Ishida, J., Yamaguchi, T., Kimura, A., Fukamizu, A., Penninger, J.M., Reversade, B., Ito, H., Imai, Y., Kuba, K.
- ID
- ZDB-PUB-170404-2
- Date
- 2017
- Source
- Cardiovascular research 113(7): 760-769 (Journal)
- Registered Authors
- Ho, Lena, REVERSADE, Bruno
- Keywords
- none
- MeSH Terms
-
- Angiotensin II*
- Animals
- Aorta/physiopathology
- Aorta/surgery*
- Apelin Receptors/deficiency
- Apelin Receptors/genetics
- Apelin Receptors/metabolism*
- Arterial Pressure
- Cardiotonic Agents/administration & dosage
- Cardiotonic Agents/pharmacology*
- Constriction
- Disease Models, Animal
- Fibrosis
- Forkhead Box Protein M1/genetics
- Forkhead Box Protein M1/metabolism
- Gene Expression Regulation
- HEK293 Cells
- Heart Failure/etiology
- Heart Failure/genetics
- Heart Failure/physiopathology
- Heart Failure/prevention & control*
- Humans
- Hypertension/genetics
- Hypertension/metabolism
- Hypertension/physiopathology
- Hypertension/prevention & control
- Hypertrophy, Left Ventricular/etiology
- Hypertrophy, Left Ventricular/metabolism
- Hypertrophy, Left Ventricular/physiopathology
- Hypertrophy, Left Ventricular/prevention & control*
- Infusions, Subcutaneous
- Ligands
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Myocardial Contraction/drug effects
- Myocardium/metabolism*
- Myocardium/pathology
- Peptide Hormones/administration & dosage
- Peptide Hormones/pharmacology*
- Peptidyl-Dipeptidase A/genetics
- Peptidyl-Dipeptidase A/metabolism
- Signal Transduction/drug effects
- Transfection
- Ventricular Dysfunction, Left/genetics
- Ventricular Dysfunction, Left/metabolism
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Dysfunction, Left/prevention & control
- Ventricular Function, Left/drug effects
- PubMed
- 28371822 Full text @ Cardiovasc. Res.
Citation
Sato, T., Sato, C., Kadowaki, A., Watanabe, H., Ho, L., Ishida, J., Yamaguchi, T., Kimura, A., Fukamizu, A., Penninger, J.M., Reversade, B., Ito, H., Imai, Y., Kuba, K. (2017) ELABELA - APJ axis protects from pressure overload heart failure and Angiotensin II-induced cardiac damage. Cardiovascular research. 113(7):760-769.
Abstract
Aims : Elabela/Toddler/Apela (ELA) has been identified as a novel endogenous peptide ligand for APJ/Apelin receptor/Aplnr. ELA plays a crucial role in early cardiac development of zebrafish as well as in maintenance of self-renewal of human embryonic stem cells. Apelin was the first identified APJ ligand, and exerts positive inotropic heart effects and regulates the renin-angiotensin system. The aim of this study was to investigate the biological effects of ELA in the cardiovascular system.
Methods and results : Continuous infusion of ELA peptide significantly suppressed pressure overload-induced cardiac hypertrophy, fibrosis and impaired contractility in mice. ELA treatment reduced mRNA expression levels of genes associated with heart failure and fibrosis. The cardioprotective effects of ELA were diminished in APJ knockout mice, indicating that APJ is the key receptor for ELA in the adult heart. Mechanistically, ELA downregulated ACE expression in the stressed hearts, whereas it showed little effects on ACE2 expression, which are distinct from the effects of Apelin. FoxM1 transcription factor, which induces ACE expression in the stressed hearts, was downregulated by ELA but not by Apelin. ELA antagonized Angiotensin II-induced hypertension, cardiac hypertrophy and fibrosis in mice.
Conclusion : The ELA-APJ axis protects from pressure overload-induced heart failure possibly via suppression of ACE expression and pathogenic Angiotensin II signaling. The different effects of ELA and Apelin on expression of ACE and ACE2 implicate fine-tuned mechanisms for a ligand-induced APJ activation and downstream signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping